Sorbinil protection of lens protein components and cell hydration during diabetic cataract formation.
Topical application of Sorbinil, a potent aldose reductase inhibitor, preserved lens growth, cell hydration and protein components--alpha, beta and gamma crystallins. The concomitant protective effects of Sorbinil were established on the three lenticular parameters because their quantitation offered a comprehensive index of lens integrity during galactose cataractogenesis. The fused eyelids of the rat neonate provided a natural delivery chamber, an orbital pouch, for topical administration of inhibitor to the treated lens; the contralateral pouch served as an untreated control. Protein preservation was determined by gel filtration chromatography. In galactose-maintained neonates, untreated lenses exhibited only 50% of the normal fraction-II component, whereas Sorbinil treatment maintained 95% of the protein. Likewise, quantitative analysis of scanning electron micrographs indicated that Sorbinil protected lenses against both intra- and extracellular fluid accumulation as determined by measurements of individual fiber cell thickness, density (the number of cells/10 micrometer cortex), and interdigitation. In addition, Sorbinil-treatment maintained normal growth as evidenced by radius and dry weight measurements. In normal neonates, Sorbinil had no effect on these parameters. These results indicate that changes in lens growth, fiber ultrastructure and protein components respond to aldose reductase inhibition by Sorbinil, thereby diminishing cataractogenesis.
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D002386:Cataract / Q000517:prevention & control*; D003459:Crystallins / Q000032:analysis*; D003930:Diabetic Retinopathy / Q000517:prevention & control*; D007093:Imidazoles / Q000627:therapeutic use*; D048289:Imidazolidines; D007908:Lens, Crystalline / Q000187:drug effects* / Q000473:pathology; D011506:Proteins / Q000032:analysis*; D051381:Rats; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D003459:Crystallins; D007093:Imidazoles; D048289:Imidazolidines; D011506:Proteins; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; C026411:sorbinil